Disease relevance of TACC1

• Using immunohistochemistry of tumor tissue-microarrays and sections, we confirm that the level of TACC1 protein is down-regulated in breast cancer [1].
• The expression of a newly identified TACC1 isoform is restricted to brain and gastric cancer tissues [2].
• Aberrations of TACC1 and TACC3 are associated with ovarian cancer [3].
• The distribution pattern of expression of the two TACC proteins was different, with TACC3 loss being more common in serous papillary carcinoma compared with clear cell carcinomas, while TACC1 staining was less frequent in endometroid than in serous papillary tumor cores [3].
• BACKGROUND: Dysregulation of the human Transforming Acidic Coiled Coil (TACC) genes is thought to be important in the development and progression of multiple myeloma, breast and gastric cancer [3].

High impact information on TACC1

• The full-length TACC proteins form similar polymers when overexpressed, but their interaction with microtubules and tubulin is regulated during the cell cycle [4].
• Transforming acidic coiled coil 1 (TACC1) is a putative oncogene located within a breast cancer amplicon found on human chromosome 8p11 [5].
• Although TACC1 has been reported to transform fibroblasts, it is also down-regulated in a subset of mammary tumors treated with anthracyclin [5].
• Thus, TACC1 positively regulates the Ras and PI3K pathways, promotes Ras-mediated transformation, and prevents apoptosis induced by PI3K pathway inhibition [5].
• TACC1 also cooperates with tumorigenic mutations in the PI3K pathway and thereby plays an oncogenic role in tumor formation in the murine mammary gland [5].

Chemical compound and disease context of TACC1

• Cyclophosphamide and/or TACC/cyclophosphamide, 6-thioguanine, cytosine arabinoside, and BCNU (BACT) were the factors basically responsible for the cardiac toxicity [6].

Biological context of TACC1

• We show that TACC1 mRNA gene expression is down-regulated in various types of tumors [1].
• Using siRNAs, we further show that depletion of chTOG and, to a lesser extent of TACC1, perturbates cell division [7].
• The TACC1 gene is located in region p12 of chromosome 8; its mRNA is ubiquitously expressed and encodes a protein with an apparent molecular mass of 125 kDa, which is cytoplasmic and mainly perinuclear [1].
• We speculate that down-regulation of TACC1 may alter the control of mRNA homeostasis in polarized cells and participates in the oncogenic processes [1].
• Using the full-length TACC1 protein as bait to screen a human mammary epithelial cDNA library, we have identified two genes that are also amplified and overexpressed in tumours derived from different cellular origins [8].

Anatomical context of TACC1

• The TACC domain identifies a family of centrosomal proteins that can interact with microtubules [4].
• Transforming acidic coiled-coil-containing protein 4 interacts with centrosomal AKAP350 and the mitotic spindle apparatus [9].
• Transforming acidic coiled-coil (TACC) proteins are centrosome and microtubule-associated proteins that are essential for mitotic spindle function [10].
• Endothelial-TACC-related mRNA was highly expressed in heart and skeletal muscle tissue [11].
• Southern blot analysis of genomic DNA from somatic cell hybrids showed that endothelial-TACC-related cDNA maps to chromosome 10 [11].

Associations of TACC1 with chemical compounds

• RESULTS: FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples [12].
• Recent, large-scale genomic analysis and Serial Analysis of Gene Expression data suggest that TACC1 and TACC3 may also be involved in the etiology of ovarian tumors from both familial and sporadic cases [3].
• Oxidant production was used as an indicator of inflammatory cell reactions and was measured by luminol-amplified chemiluminescence after treatment with inflammatory activators including bacteria, the neutrophil taxin formyl-Met-Leu-Phe, the Ca2+ ionophore A23187, the detergent saponin, and the tumor promoter phorbol ester [13].
• The pregraft regimen was cyclophosphamide, 6-thioguanine, cytosine arabinoside, and CCNU (TACC) in 39 cases, cyclophosphamide (CY) associated with whole-body irradiation in 16 cases, and multiple chemotherapeutic agents in 8 cases [6].
• All patients received BACT (BCNU+aracytine+cyclophosphamide+thioguanine) or TACC (idem with CCNU) at different dose levels: 6/17 received 10 Gy total-body irradiation (TBI) after BACT treatment; 16/17 received autologous bone marrow transplantation (ABMT) previously stored in liquid nitrogen to combat the medullary effects of chemotherapy [14].

Physical interactions of TACC1

• GST pull-down analysis subsequently confirmed that all human TACC family members can bind in vitro to hGCN5L2 [15].

Regulatory relationships of TACC1

• Recent studies show that Aurora A kinase promotes microtubule assembly from centrosomes through the phosphorylation of the conserved centrosomal protein TACC [16].

Other interactions of TACC1

• AINT/ERIC/TACC: an expanding family of proteins with C-terminal coiled coil domains [17].
• Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains [17].
• Using AKAP350A as bait in a yeast two-hybrid screen of a rabbit parietal cell library, we have identified a novel AKAP350-interacting protein, transforming acidic coiled-coil-containing protein 4 (TACC4) [9].
• We further show that Aurora B knocked down by RNA-mediated interference prevents the formation of the midbody - and consequently affects TACC1 localization at this site - and leads to abnormal cell division and multinucleated cells [18].
• However, during evolution, the TACC proteins have now acquired the ability to directly interact with components of these complexes (such as the LSm proteins, nuclear hormone receptors, GAS41, and transcription factors) [19].

Analytical, diagnostic and therapeutic context of TACC1

• Using real-time PCR, we quantitated the mRNA levels of TACC3 compared to TACC1 and TACC2 in various human adult tissues [20].
• The 5'RLM-RACE and reverse transcriptase polymerase chain reaction analyses revealed at least six different transcript variants of TACC1 with variable transcription start sites and alternative exon usage (designated TACC1-A-TACC1-F) [10].
• We suggest, therefore, that the transplantation should be done as early as possible and preference should be given whenever possible to whole-body irradiation over high-dose chemotherapy combinations such as TACC [6].
• A percentage decrease in triceps skinfold was significantly greater in the TACC group than in the control group [21].

References